biomarkers and heart failure: application and limitation › intermountaincme... · biomarker &...

Biomarkers and Heart Failure: Application and Limitation

Rami Alharethi, MD FACC

Biomarker & Heart Failure

• A biomarker should fulfill all the following criteria to be useful clinically:

1. Accurate, reproducible, reasonable cost, and short turnaround time.

2. Provide information that is not available from clinical assessment

3. Will aid in medical decision making

Natriuretic Peptides & Heart Failure

Pro-hBNP

BNP NTproBNP

• Natriuretic, diuretic, and vasodilatory • Inhibit RAAS, SNS, and endothelin 1

BNP and HF diagnosis

N Engl J Med 2002;347:161-7

BNP & Heart Failure Prognosis

J Am Coll Cardiol 2004;43:635– 41

NT ProBNP & Screening healthy population

J Am Coll Cardiol 2010;55:2140–7

NT-proBNP Guided Therapy

JAMA. 2009;301(4):383-392 JAMA. 2009;301(4):383-392 JAMA. 2009;301(4):383-392

NT-proBNP Guided Therapy

JAMA. 2009;301(4):383-392

NT-proBNP Guided Therapy

JAMA. 2009;301(4):383-392

Biomarker & Heart Failure

BNP and NT ProBNP levels

False Positive False Negative •Pulmonary HTN •Pulmonary embolism •Renal dysfunction •Rapid decrease pcw •Older ager •Female Gender •ACS

•Flash pulmonary edema •Acute MR •Obesity

Natriuretic Peptides & Heart Failure

BNP and NT-proBNP concentrations vary with the assay used, age, sex, and body mass index and renal function.

Plasma BNP or NT-proBNP is useful as a component of the evaluation of suspected heart failure (HF) when the diagnosis is uncertain.

Randomized trials studying the effect of BNP- or NT-proBNP guided therapy on clinical outcomes have shown mixed results.

Natriuretic Peptides & Heart Failure

The value of serial BNP measurement in guiding management of acute HF has not been established. Plasma BNP and NT-proBNP provide

prognostic information in patients with acute and chronic HF, and plasma BNP has prognostic value in those with asymptomatic or minimally symptomatic LV dysfunction

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Initial Clinical Assessment of Patients Presenting With Heart Failure

Measurement of natriuretic peptides (B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proNBP)) can be useful in the evaluation of patients presenting in the urgent care setting in whom the clinical diagnosis of HF is uncertain. Measurement of natriuretic peptides (BMP and NT-proBNP) can be helpful in risk stratification.

Measurement of BNP

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

The value of serial measurements of BNP to guide therapy for patients with HF is not well established

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Trop I and T in ADHF

N Engl J Med 2008;358:2117-26

• 4053 patients from Val-HeFT and 1231 patients from GISSI-HF were included in the analysis. In the two trials, hs-cTnT was measured at baseline and at four and three months, respectively.

Troponin T & Heart Failure

sST2 Novel Biomarker & HF

ST2 is a novel biomarker, a peptide from the Interleukin (IL)-1 receptor family.

It was found by gene transcripts induced by mechanically stressed cardiomyocytes in vitro .

ST2 exists as membrane binding form (ST2L) and as soluble form (sST2), both are up-regulated in cardiomyocytes and fibroblasts exposed to biomechanical stress.

Biomarker & Heart Failure

Circ Heart Fail. 2009;2:311-319.

Galactin 3 and Heart Failure

• Galectin-3 is a b-galactoside-binding lectin overexpressed by macrophages during phagocytosis, with an emerging, critical role in fibrosis within the heart.

• Galectin-3 is an integrated pathophysiologic signal for myocardial fibrosis, ventricular dysfunction.

Galectin-3 Levels Changes & Chronic HF •A

biomarker should fulfill all the following criteria to be us

Circ Heart Fail. 2013 Mar;6(2):219-26

Galectin-3 Levels Changes & Chronic HF •A

biomarker should fulfill all the following criteria to be us

Circ Heart Fail. 2013 Mar;6(2):219-26

Biomarker & Heart Failure

• BNP/NTproBNP are useful in diagnosis HF when clinically is not clear.

• Elevated BNP/NTproBNP are associated with worse prognosis.

• BNP/NTproBNP guided therapy is not yet proven to improve outcome.

• The role of new “novel” biomarkers in the clinical practice still need to be investigated.